Beyond type 2 asthma biomarkers: risk stratification for NSAID-exacerbated respiratory disease.

Introduction: Type 2 (T2) asthma is often associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Additionally, nonsteroidal anti-inflammatory drug (NSAID) intolerance leads to NSAID-exacerbated respiratory disease (N-ERD). Previous transcriptomic data in non-CRSwNP T2 asthma patients showed differentially expressed genes. We focused on ALOX15, CLC, CYSLTR2, HRH4 and SMPD3 to investigate their role in T2 asthma. Methods: The study included 100 healthy controls and 103 T2 asthma patients, divided into patients with asthma (n=54), patients with asthma and CRSwNP (n=29) and patients with N-ERD (n=20). Quantitative PCR analysis was performed on blood-derived RNA samples first to validate the five differentially expressed genes. The data were further analysed to find potential associations and biomarkers. Results: Patients, regardless of stratification, exhibited significantly higher gene expression than healthy controls. The patterns of association revealed that ALOX15 was exclusively present in the non-comorbidity group, SMPD3 and CLC in the comorbidity groups, and HRH4 in all patient groups. ALOX15, CYSLTR2 and SMPD3 expression showed potential as biomarkers to confirm the diagnosis of T2 asthma using peripheral blood eosinophils as the initial criterion. Peripheral blood eosinophils combined with gene expression, especially SMPD3, may improve the diagnosis. CLC and CYSLTR2 expression play a specific role in discriminating N-ERD. Discussion: We validated the transcriptomic data of five differentially expressed genes in T2 asthma. Different patterns of association were identified in patient stratification, suggesting that different molecular mechanisms underlie the spectrum of T2 asthma. Potential biomarkers were also found and used to design an algorithm with practical diagnostic utility for T2 asthma, including risk stratification for N-ERD.

Delabeling of allergy to beta-lactam antibiotics in hospitalized patients: a prospective study evaluating cost savings.

BACKGROUND: Patients with a penicillin allergy label are at risk of an associated increase in adverse antibiotic events and hospitalization costs. AIM: We aimed to study the economic savings derived from the correct diagnosis and delabeling inpatients with suspected beta-lactam allergy, considering the acquisition cost of antimicrobials prescribed during a patient's hospital stay. METHOD: We prospectively evaluated patients admitted to the University Hospital of Salamanca who had been labeled as allergic to beta-lactams and performed a delabeling study. Subsequently, cost differences between antibiotics administered before and after the allergy study and those derived from those patients who received alternative antibiotics during admission and those who switched to beta-lactams after the allergy study were calculated. RESULTS: One hundred seventy-seven inpatients labeled as allergic to beta-lactams underwent a delabeling study; 34 (19.2%) were confirmed to have allergy to beta-lactams. Of the total number of patients, 136 (76.8%) received antibiotics during their hospitalization, involving a mean (SD) cost of €203.07 (318.42) and a median (IQR) cost of €88.97 (48.86-233.56). After delabeling in 85 (62.5%) patients, the antibiotic treatment was changed to beta-lactams. In this group of patients, the mean cost (SD) decreased from €188.91 (351.09) before the change to 91.31 (136.07) afterward, and the median cost (IQR) decreased from €72.92 (45.82-211.99) to €19.24 (11.66-168). The reduction was significant compared to the median cost of patients whose treatment was not changed to beta-lactams (p<0.001). CONCLUSION: Delabeling hospitalized patients represents a cost-saving measure for treating patients labeled as allergic to beta-lactams.

Can rare earth elements be recovered from abandoned mine tailings by means of electrokinetic-assisted phytoextraction?

Given the high impact of traditional mining, the recovery of rare earth elements (REEs) from hazardous waste materials could become an option for the future in accordance with the principles of the circular economy. In this work, the technical feasibility of REEs recovery from metal mine tailings has been explored using electrokinetic-assisted phytoremediation with ryegrass (Lolium perenne L.). Phytoextraction combined with both AC current and DC current with reversal polarity was applied (1 V cm-1, 8 h day-1) to real mine tailings containing a total concentration of REEs (Sc, Y, La, Ce, Pr, and Nd) of around 146 mg kg-1. Changes in REEs geochemical fractionation and their concentrations in the soil pore water showed the mobilization of REEs caused by plants and electric current; REE availability was increased to a higher extent for combined electrokinetic-assisted phytoextraction treatments showing the relevant role of plants in the process. Our results demonstrated the initial hypothesis that it is feasible to recover REEs from real metal mining waste by phytoextraction and that the performance of this technology can be significantly improved by applying electric current, especially of the AC type, which increased REE accumulation in ryegrass in the range 57-68% as compared to that of the treatment without electric field application.

A new hyperaccumulator plant (Spergularia rubra) for the decontamination of mine tailings through electrokinetic-assisted phytoextraction.

The screening of new effective metal hyperaccumulators is essential for the development of profitable phytoremediation projects in highly degraded environments such as mining areas. The goal of this research was to analyze the phytoextraction potential of the native plant Spergularia rubra to decontaminate and eventually recover metals (phytomining) from the mine tailings (belonging to an abandoned Pb/Zn Spanish mine) in which it grows spontaneously. To do so, the ability of this plant species to accumulate metals was evaluated both under natural conditions and through simple and electrokinetically assisted phytoextraction tests using alternating current and different combinations of voltage gradient (1/2 V cm-1) and application time (6/12 h per day). The complete duration of the greenhouse trial was 64 days, although alternating current was applied only during the last 14 days. The results obtained demonstrated the exceptional effectiveness of S. rubra for metal hyperaccumulation and growth without affecting toxicity in highly contaminated mining waste. Zn was the metal accumulated to a higher extent in the shoots, reaching concentrations up to 17,800 mg kg-1; Pb was mainly accumulated in the roots reaching a maximum concentration of 8709 mg kg-1. Cu and Cd were accumulated to a lesser extent but the bioconcentration factors were much >1. It has been proved that S. rubra is a hyperaccumulator species for Zn and Cd both in natural and greenhouse conditions and, very probably, Pb in wild conditions. The application of AC current did not significantly increase metal concentrations in plant tissues but it was able to increase the aerial biomass of S. rubra by 49.8 %. As a result, the phytoextraction yields of all metals were significantly improved as compared to wild conditions (up to 86 % for Zn). It could open new expectations about the economic viability of recovering high-value metals from mine tailings.

A novel approach for venous occlusion after endocavitary leads. The balloon-assisted tracking technique.

The balloon-assisted tracking technique can be useful in short venous occlusions that conventional venoplasty fails. This technique could be feasible and with an expected low complication rate.

Report of two sisters with Netherton syndrome successfully treated with dupilumab and review of the literature.

Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40 subunit of IL-12 and IL-23), omalizumab (anti-IgE), and dupilumab (anti-IL4 and IL13). We report two sisters with severe NS who were treated with omalizumab in one and with secukinumab in the other. In view of the therapeutic failure, treatment with dupilumab was started in both sisters. The data were analyzed 16 weeks after starting treatment with dupilumab. Treatment response was assessed using the Severity Scoring Atopic Dermatitis (SCORAD); Eczema Area and Severity Index (EASI); Pruritus Numeric Rating Scale (NSR); Netherton Area Severity Assessment (NASA) and Dermatology Life Quality Index Ichthyosis. All scores were reduced after 16 weeks of treatment with dupilumab in both patients. She maintains improvement after 18 months and 12 months of treatment, respectively. No severe adverse events were reported. Treatment with dupilumab in two sisters with NS and atopic diseases produced a marked cutaneous improvement after a failed attempt with omalizumab and secukinumab. Further studies are needed to determine which biologic therapy is the most effective in NS.

A classical modelling of abandoned mine tailings' bioleaching by an autochthonous microbial culture.

The aim of this study was to study and model the bioleaching of abandoned mine tailings at different pulp densities 1-20% w/v by using an autochthonous mesophilic microbial culture. Because of the importance of the ferrous-iron oxidation as sub-process on the bioleaching of sulphide mineral ores, the ferrous-iron oxidation process by the autochthonous microbial culture was studied at different ferrous-iron concentrations. A mathematical model fitted to the experimental results and the main kinetic and stoichiometric parameters were determined, being the most relevant the maximum ferrous-iron oxidation rate 5.1 (mmol Fe2+/mmol C·h) and the biomass yield, 0.01 mmol C/mmol Fe2+, values very similar to that of mixed cultured dominated by Leptospirillum strains. This autochthonous culture was used in the bioleaching experiment carried out at different pulp densities, obtaining a maximum metal recovery in the tests carried out at 1% w/v, recovering a 90% of Cd, 60% of Zn, 30% of Cu, 25% Fe and 6% of Pb. Finally, the different leaching mechanisms were modelled by using the pyrite as ore model obtaining a bioleaching rate of 0.316 mmol Fe2+/(L·h) for the direct mechanisms and a bioleaching rate for the indirect and cooperative leaching mechanisms of 0.055 Fe2+/(L·h).

Changes in Sensitization Patterns in the Last 25 Years in 619 Patients with Confirmed Diagnoses of Immediate Hypersensitivity Reactions to Beta-Lactams.

Beta-lactam (BL) drugs are the antibiotics most prescribed worldwide due to their broad spectrum of action. They are also the most frequently implied in hypersensitivity reactions with a known specific immunological mechanism. Since the commercialization of benzylpenicillin, allergic reactions have been described; over the years, other new BL drugs provided alternative treatments to penicillin, and amoxicillin is now the most prescribed BL in Europe. Diagnosis of BL allergy is mainly based on skin tests and drug provocation tests, defining different sensitization patterns or phenotypes. In this study, we evaluated 619 patients with a confirmed diagnosis of BL-immediate allergy during the last 25 years, using the same diagnostic procedures with minor adaptations to the successive guidelines. The initial eliciting drug was benzylpenicillin, which changed to amoxicillin with or without clavulanic acid and cephalosporins in recent years. In skin tests, we found a decrease in sensitivity to major and minor penicillin determinants and an increase in sensitivity to amoxicillin and others; this might reflect that the changes in prescription could have influenced the sensitization patterns, thus increasing the incidence of specific reactions to side-chain selective reactions.

Hypersensitivity to Gadolinium-Based Contrast Media.

Gadolinium-based contrast agents (GBCAs) are frequently used in magnetic resonance imaging (MRI) examinations to increase sensitivity in diagnoses. Recently, an increase in the description of hypersensitivity reactions to GBCAs has been detected. We performed research in PubMed, PubMed, SCOPUS, and EMBASE until September 2021, searching for studies regarding immediate and delayed hypersensitivity reactions to gadolinium-based contrast agents in which an allergy study was performed. The initial research identified 149 articles written in English. After excluding articles duplicated and articles that had irrelevant designs, 26 articles were included. Finally, 17 studies concerning immediate reactions, six studies concerning non-immediate reactions, and three concerning both that performed allergy evaluations were selected. In the review, we analyzed the characteristics of immediate and delayed reactions and the results of the allergy study and cross-reactivity. Skin tests seem to have acceptable accuracy, but drug provocation tests are still needed when skin tests are negative o to find alternative agents. Although cross-reactivity patterns are not well established, cross-reactivity seems to exist among macrocyclic agents. Notwithstanding, the number of patients analyzed is low and further studies are required. A management algorithm is suggested.

Does environmental risk really change in abandoned mining areas in the medium term when no control measures are taken?

Studies regarding how environmental risk evolves in abandoned mining areas in the medium term have been seldom carried out. The answer to this question is not obvious despite it is essential in order to evaluate the need to take urgent control measures in these areas. Fifty-two samples corresponding to soils (from natural pasture and arable lands) and mine tailings were collected in the surroundings of an old Spanish Pb/Zn mine (San Quintín, Central Spain). Current concentrations of pseudo-total and available metal (loid)s (Pb, Zn, Cd, Cu, As and Ag) were determined and the environmental risk assessment (ERA) was conducted with these data and those corresponding to a sampling previously carried out in 2006. ERA was carried out by calculating the geoaccumulation index (Igeo), the pollution load index (PLI) and the potential ecological risk index (PER). Results demonstrated that Pb and Zn concentrations have increased in the soils of the plots surrounding the mining areas causing a moderate rise in most of the determined pollution indices between 2006 and 2020. It was especially significant in the pastureland areas, with increases up to 17% in the number of soil samples that reached the highest risk classification in 2020 as compared to those taken in 2006. The results obtained here demonstrate that the environmental risk can actually increase in a continuous way in abandoned mining areas despite the closure of the mining operation and the effect of the possible natural attenuation.

Angioedema Due to Acquired Deficiency of C1-Inhibitor: A Cohort Study in Spain and a Comparison With Other Series.

BACKGROUND: Data on acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) from 4 European countries (France, Italy, Germany, and Hungary) were recently published. OBJECTIVE: To report data from a group of 50 patients with acquired C1-INH deficiency from Spain, of whom 46 had angioedema, and compare them with other European series. METHODS: We performed a retrospective observational study of 46 patients with C1-INH-AAE and 4 asymptomatic patients. Clinical and biological characteristics and associated diseases were assessed and compared with other European series. RESULTS: Women accounted for 73.9% of cases. The prevalence of C1-INH-AAE related to hereditary forms was 1/10.1. Overall, 8.7% patients were aged <40 years. Diagnostic delay was 1.1 years. Angioedema mainly affected the face (91.3%), followed by the oropharynx (63%), extremities (50%), and abdomen (37%). Only 1 patient underwent orotracheal intubation. Erythema marginatum was present in 1 patient. A hematologic disorder was recorded in 50% of patients. Angioedema preceded all benign conditions, mostly monoclonal gammopathy of undetermined significance, but appeared very close to or after malignant hematologic diseases (median, 2.2 and 0.29 years). Autoimmune diseases were associated in 50% (autoimmune thyroiditis, 21.5%; systemic lupus erythematosus, 10.9%). Half of them coexisted with hematologic disorders. Anti-C1-INH antibodies were found in 67% of tested patients and were not related to the associated disease. Long-term prophylaxis was necessary in 52.2%, most of whom responded to tranexamic acid. CONCLUSIONS: This study emphasizes the possibility of C1-INH-AAE in patients younger than 40 and in autoimmune diseases other than systemic lupus erythematosus such as autoimmune thyroiditis.

Impact on daily clinical practice of the latest evidence on percutaneous closure of patent foramen ovale after cryptogenic stroke: a single-center experience.

INTRODUCTION AND OBJECTIVES: At the end of 2017, three clinical trials demonstrated that, in selected patients, percutaneous closure of patent foramen ovale (PFO) after cryptogenic stroke (CS) reduces the risk of recurrence. Our aim was to determine the impact of these findings on routine clinical practice in a tertiary hospital. METHODS: Patients with CS and percutaneous closure of PFO during 2001-2020 were included. The clinical characteristics of the patient and the anatomical characteristics of the foramen were analyzed. Based on both, the closure indications were classified into three groups according to the latest European recommendations and were analyzed in two periods, before and after the publication date of the clinical trials. RESULTS: A total of 293 patients were included. The mean age was 49 ± 11 years, and 15% were older than 60 years. The median RoPE score was 6 [p25-75, 5-7] and 75% had complex anatomy (CA). After the publication of the studies, the frequency of CA and the mean age of the patients were significantly higher (89% vs. 69% p < 0.0005 and 51 ± 11 vs. 48 ± 11 years, p = 0.02, respectively), and the RoPE score, significantly lower (5 [5-7] versus 6 [5-7], p = 0.02). Inadequate closure indications were significantly reduced (8% vs. 18%, p = 0.02). CONCLUSION: After the publication of clinical trials that have shown benefit of PFO closure after CS, the number of inappropriate indications for closure has decreased significantly in our institution, with a higher percentage of CA, despite a clinical profile suggestive of lower causal probability of PFO.

Usefulness of an Artificial Neural Network in the Prediction of ß-Lactam Allergy.

BACKGROUND: An accurate diagnosis of ß-lactam (BL) allergy improves the use of antibiotics, increases patients' safety, and reduces costs to health systems. Nevertheless, it requires skin and drug provocation tests, which are time-consuming and put the patient at risk. Furthermore, allergy testing is not available in circumstances such as the urgent need for antibiotic therapy. OBJECTIVE: To evaluate the usefulness of an artificial neural network (ANN) in the prediction of hypersensitivity to BLs, and compare it with logistic regression (LR) analysis. METHODS: In a single-center study, 656 patients evaluated for BL allergy between 1994 and 2000 were retrospectively analyzed, and the data were used to construct an ANN. The ANN predictive capabilities were compared with LR and then prospectively evaluated in 615 patients who underwent BL evaluation between 2011 and 2017. RESULTS: A total of 1271 patients were evaluated. All patients had a definite diagnosis as allergic or nonallergic to BL. The prospective sample showed a lower percentage of patients with allergy than the retrospective sample (20.7% vs 25.8%; P = .018). In the retrospective and prospective series, the ANN reached a sensitivity of 89.5% and 81.1%, a specificity of 86.1% and 97.9%, a positive predictive value of 82.1% and 91.1%, and a negative predictive value of 92.1% and 95.2%, respectively. The ANN's performance was far superior to that of the LR, whose best performance reached a sensitivity of 31.9% and a specificity of 98.8%. CONCLUSIONS: This ANN demonstrated a superior performance than the LR in predicting BL hypersensitivity without misdiagnosing severe allergic reactions. The ANN could be a helpful tool to classify the reaction risk, particularly in the identification of low-risk patients, in which an open challenge could be done to delabel patients.

A Prospective Study of Costs Associated with the Evaluation of ß-Lactam Allergy in Children.

OBJECTIVE: To evaluate the costs associated with evaluation of ß-lactam allergy in children labeled as allergic. STUDY DESIGN: We performed a prospective year-long real life observational study designed to evaluate all pediatric patients with suspected ß-lactam allergy who consulted for allergy evaluation. Direct and indirect costs were systematically recorded. Direct healthcare costs were calculated by taking into account the number of visits and all complementary and diagnostic tests performed. Direct nonhealthcare costs were calculated by considering the number of visits and the kilometers from their homes to the clinic. Finally, indirect costs were evaluated by considering the absenteeism of parents or other companions who took the children to the clinic. RESULTS: A total of 40 children with suspected allergy to ß-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct healthcare costs were $5038.03, with an average cost per patient of $125.95. Direct nonhealthcare costs reached $901.87 ($22.55 per patient) and indirect nonhealthcare costs reached $6384.35 ($159.61 per patient). The total cost was $12 324.25, a cost of $308.11 per patient. CONCLUSIONS: Elective evaluation of ß-lactam allergy and delabeling children who are not allergic is not expensive. In addition, it could save future expenses because of an unnecessary lifelong use of alternative antibiotics that are usually more expensive, less effective, and more frequently associated with antimicrobial resistance and different side effects.