Basophil activation test is a complementary tool in the diagnosis of immediate reactions to platinum salts and taxanes

Background Delabelling pathways offer confirmatory diagnosis and can prevent unnecessary second-line therapies or drug desensitization procedures after chemotherapeutic hypersensitivity reactions (CHT-HSRs). However, these pathways rely on risky in vivo tests. Data on whether in vitro tests could be helpful are scarce. We assessed the role of basophil activation test (BAT) in the diagnosis of HSRs to platin salts (PSs) and taxanes (TXs) in a well-defined population featuring varied endophenotypes and severities of HSRs. Methods We conducted a 3-year-long multicentric, prospective study with 121 suspected-immediate CHT-HSR patients. The allergy workup included clinical history (initial reaction based on Type I, cytokine release syndrome, and mixed phenotype's symptoms and if unable to fit in any of these, as “indeterminate”), skin testing (ST), and drug provocation testing (DPT), provided risk assessment was favorable. Final diagnosis classified patients as “hypersensitive,” “non-hypersensitive,” or “inconclusive.” We performed BAT using CD63 and CD203c as activation markers in patients and controls. Patients underwent DPT regardless of BAT results to prevent bias. Results ST positivity significantly correlated with skin involvement, Type I phenotype, cancer recurrence, and lifetime exposures before reactions. DPTs were negative in all indeterminate phenotype patients (p = .02) and those considered low-risk, whereas they were negative in 62% moderate-risk patients. 55% were confirmed as hypersensitive (mainly Type I reactions, p < .0001), 24% as non-hypersensitive (mainly TXs and indeterminate phenotypes), and 21% as inconclusive. BAT showed 79% sensitivity in Type I IgE-mediated reactions to PSs with a high correlation to ST.Funding for open access charge: Universidad de Málaga / CBUA. This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Ministry of Economy and Competitiveness (MINECO), grants co-founded by Fondo Europeo de Desarrollo Regional—FEDER for the Thematic Networks and Co-operative Research Centres: PI22/01119; PI18/00095; RETICS ARADYAL RD16/0006/0001, RICORS REI (RD21/0002/0008); Biobank network RD09/0076/00112; Biobank platform PT13/0010/0006; Andalusian Regional Ministry of Economy and Knowledge (grants PI-0076-2019). G.B. is a clinical investigator (B-0007-2022), research contract by Andalusian Regional Ministry Health. A.A. thanks Senior Postdoctoral Contract (RH-0099-2020) from Andalusian Regional Ministry of Health (co-funded by European Social Fund [ESF]: “Andalucía se mueve con Europa”) and “Nicolas Monardes” research contract by Andalusian Regional Ministry Health (C1-0007-2023). CLM holds a P-FIS contract (FI23/00027) by ISCIII. SCS holds a predoctoral contract by Andalusian Regional Goverment (PREDOC_01545). CM holds a “Nicolas Monardes” research contract by Andalusian Regional Ministry Health (RC-0004-2021)

Evaluación de las características fisicoquímicas y sensoriales del pan de molde enriquecido con Kiwicha (Amaranthus caudatus L.) y Cañihua (Chenopodium pallidicaule Aellen)

Bread is a widely consumed food, which has wheat as its basic ingredient; there are various formulations that include flour from different cereal sources. The objective of the research was to evaluate the effect of including Kiwicha (Amaranthus caudatus L.) and Cañihua (Chenopodium pallidicaule Aellen) on the physicochemical and sensory characteristics of bread leaf. The preparation of ​​bread leaf was developed with the direct dough method; the mixture was carried out with a simple mixture design and only the three formulations with the highest protein contents were selected., F1(trigo, Kiwicha, Cañihua: 73 %, 17 %, 10 %); F2 (wheat, Kiwicha, Cañihua: 73 %, 20 %, 7 %) and F3 (wheat, Kiwicha, Cañihua: 70%, 20%, 10%); F0 was considered as control: bread leaf made with 100% wheat flour. The physicochemical characteristics were analyzed using a complete randomized design (RCD), with Tukey's test (p ≤ 0,05) and sensory properties with Friedman's test (p ≤ 0,05). The results showed that the physicochemical characteristics were different (p ≤ 0,05) except for pH and titratable acids. The F3 formulation reported lower alanine content and higher leucine content with 0,10 to 1,79 g of amino acid (AA) per 100 g of protein pure, determined in (g/100 g of original sample and factor 6,25), respectively. In the bread crust, the L* color analysis was higher in formulation F3 (50,0) (p ≤ 0,05) while the other formulations F1 and F2 varied. Sensorily, the F0 treatment had greater acceptability, however, in the prepared breads (F1, F2 and F3) the content of iron, amino acids and macronutrients stands out. It is concluded that breads made with the addition of Kiwicha and Cañihua to the flour formulation are a good source of proteins, iron, and amino acids.El pan es un alimento de consumo masivo, que tiene como ingrediente básico al trigo; existen diversas formulaciones en la que incluyen harina de distintas fuentes de cereales. El objetivo de la investigación fue evaluar el efecto de la inclusión de Kiwicha (Amaranthus caudatus L.) y Cañihua (Chenopodium pallidicaule Aellen) en las características fisicoquímicas y sensoriales del pan de molde. La elaboración del pan de molde se desarrolló con el método de masa directa; la mezcla se realizó con diseño de mezclas simples y se seleccionaron solo las tres formulaciones con los contenidos más altos de proteínas, F1 (trigo, Kiwicha, Cañihua: 73 %, 17 %, 10 %); F2 (trigo, Kiwicha, Cañihua: 73 %, 20 %, 7 %) y F3 (trigo, Kiwicha, Cañihua: 70 %, 20 %, 10 %); se consideró como control F0: pan de molde elaborado con 100 % de harina de trigo. Las características fisicoquímicas se analizaron mediante diseño completo al azar (DCA), con prueba de Tukey (p ≤ 0,05) y las propiedades sensoriales se analizaron con la prueba de Friedman (p ≤ 0,05). Los resultados mostraron que las características fisicoquímicas fueron diferentes (p ≤ 0,05), a excepción del pH y acidez titulable. La formulación F3, reportó menor contenido de alanina y mayor cantidad leucina con 0,10 a 1,79 g de aminoácido (AA) por 100 g de proteína pura, determinada en (g/100 g de muestra original y factor 6,25), respectivamente. En la corteza de pan, el análisis de color L* fue mayor en la formulación F3 (50,0) (p ≤ 0,05) mientras que las otras formulaciones variaron F1 y F2. Sensorialmente, el tratamiento F0 tuvo mayor aceptabilidad, sin embargo, en los panes elaborados (F1, F2 y F3) se destaca el contenido de hierro, aminoácidos y macronutrientes. Se concluye que los panes elaborados con adición de Kiwicha y Cañihua a la formulación de la harina son una buena fuente de proteínas, hierro y aminoácidos

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

New Advances in Optical Coherence Tomography

La Tomografía de Coherencia Óptica (OCT) es una técnica de diagnóstico por la imagen no invasiva y de no contacto que permite realizar cortes tomográficos micrométricos de la retina con una alta sensibilidad. Desde su desarrollo en 1991, numerosas investiga ciones han sido llevadas a cabo para mejo rar la resolución, la velocidad de adquisición de imágenes e incluso su funcionalidad. En la práctica clínica estas mejoras hacen posible la realización de un examen de la retina en tiempo real que aporta mayor in formación que la OCT convencional. En este artículo se revisan los avances más recientes en este campo.Depto. de Optometría y VisiónFac. de Óptica y OptometríaTRUEpubPagado por el auto

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons