Spirometry and respiratory oscillometry: Feasibility and concordance in schoolchildren with asthma.

OBJECTIVE: The purpose of this study was to describe the feasibility of respiratory oscillometry (RO) in schoolchildren with asthma, and the concordance of its results with those of spirometry, to determine its clinical usefulness. METHODS: RO and spirometry were performed in 154 children (6 to 14-year-old) with asthma, following strict quality criteria for the tests. Their feasibility (probability of valid test, time of execution, number of maneuvers needed to achieve a valid test, and perceived difficulty) was compared. The factors that influence feasibility were analyzed with multivariate methods. FEV1, FEV1/FVC, FVC and FEF25-75 for spirometry, and R5, AX and R5-19 for RO, were converted into z-scores and their concordance was investigated through intraclass correlation coefficients (ICC) and kappa indices for normal/abnormal values. RESULTS: There were no differences in the probability of obtaining a valid RO or spirometry (83.1% vs. 81.8%, p = 0.868). RO required a lower number of maneuvers [mean (SD) 4.2 (1.8) versus 6.0 (1.6), p < 0.001] and less execution time [5.1 (2.7) versus 7.6 (2.4) minutes, p < 0.001], and patients considered it less difficult. Age increased the probability of obtaining valid RO and spirometry. The concordance of results between RO and spirometry was low, and only between zFEV1 and zAX could it be considered moderate (ICC = 0.412, kappa = 0.427). CONCLUSION: RO and spirometry are feasible in children with asthma. RO has some practical advantages, but the concordance of its results with spirometry is low.

Impact of genetic structural variants in factor XI deficiency: identification, accurate characterization, and inferred mechanism by long-read sequencing.

BACKGROUND: Congenital factor XI (FXI) deficiency is a probably underestimated coagulopathy that confers antithrombotic protection. Characterization of genetic defects in F11 is mainly focused on the identification of single-nucleotide variants and small insertion/deletions because they represent up to 99% of the alterations accounting for factor deficiency, with only 3 gross gene defects of structural variants (SVs) having been described. OBJECTIVES: To identify and characterize the SVs affecting F11. METHODS: The study was performed in 93 unrelated subjects with FXI deficiency recruited in Spanish hospitals over a period of 25 years (1997-2022). F11 was analyzed by next-generation sequencing, multiplex ligand probe amplification, and long-read sequencing. RESULTS: Our study identified 30 different genetic variants. Interestingly, we found 3 SVs, all heterozygous: a complex duplication affecting exons 8 and 9, a tandem duplication of exon 14, and a large deletion affecting the whole gene. Nucleotide resolution obtained by long-read sequencing revealed Alu repetitive elements involved in all breakpoints. The large deletion was probably generated de novo in the paternal allele during gametogenesis, and despite affecting 30 additional genes, no syndromic features were described. CONCLUSION: SVs may account for a high proportion of F11 genetic defects implicated in the molecular pathology of congenital FXI deficiency. These SVs, likely caused by a nonallelic homologous recombination involving repetitive elements, are heterogeneous in both type and length and may be de novo. These data support the inclusion of methods to detect SVs in this disorder, with long-read-based methods being the most appropriate because they detect all SVs and achieve adequate nucleotide resolution.

Contact pathway in surgical and transcatheter aortic valve replacement.

Background: Aortic valve replacement is the gold standard treatment for severe symptomatic aortic stenosis, but thrombosis of bioprosthetic valves (PVT) remains a concern. Objective: To analyze the factors involved in the contact pathway during aortic valve replacement and to assess their impact on the development of thromboembolic complications. Methods: The study was conducted in 232 consecutive patients who underwent: transcatheter aortic valve replacement (TAVR, N = 155), and surgical valve replacement (SAVR, N = 77) (MUVITAVI project). Demographic and clinical data, outcomes including a combined end point (CEP) of thrombotic events, and imaging controls were recruited. Samples were collected 24 h before and 48 h after valve replacement. FXII, FXI and (pre)kallikrein were evaluated by Western Blot and specific ELISA with nanobodies. Results: The CEP of thrombotic events was reached by 19 patients: 13 patients presented systemic embolic events and 6 patients subclinical PVT. Valve replacement did not cause FXII activation or generation of kallikrein. There was a significant reduction of FXI levels associated with the procedure, which was statistically more pronounced in SAVR than in TAVR. Cases with reductions of FXI below 80% of basal values had a lower incidence of embolic events during the procedure than patients in whom FXI increased above 150%: 2.7 vs. 16.7%; p: 0.04. Conclusion: TAVR or SAVR did not significantly activate the contact pathway. A significant reduction of FXI, was observed, particularly in SAVR, associated with lower incidence of thrombotic events. These results encourage evaluating the usefulness and safety of FXI-directed antithrombotic treatments in these patients.

Self-Consistent Mean Field Calculations of Polyelectrolyte-Surfactant Mixtures in Solution and upon Adsorption onto Negatively Charged Surfaces.

Self-Consistent Mean-Field Calculations (SCF) have provided a semi-quantitative description of the physico-chemical behavior of six different polyelectrolyte-surfactant mixtures. The SCF calculations performed showed that both the formation of polymer-surfactant in bulk and the adsorption of the formed complexes onto negatively-charged surfaces are strongly affected by the specific nature of the considered systems, with the polymer-surfactant interactions playing a central role in the self-assembly of the complexes that, in turn, affects their adsorption onto interfaces and surfaces. This work evidences that SCF calculations are a valuable tool for deepening on the understanding of the complex physico-chemical behavior of polyelectrolyte-surfactant mixtures. However, it is worth noting that the framework obtained on the basis of an SCF approach considered an equilibrium situation which may, in some cases, be far from the real situation appearing in polyelectrolyte-surfactant systems.

Recidiva de melanoma en gestación / Melanoma recurrence and pregnancy

La incidencia de melanoma durante el embarazo es del 0,1 al 2,8/1.000 partos. En mujeres con antecedente de melanoma, la gestación no parece aumentar el riesgo de recurrencia ni tener efectos adversos sobre la supervivencia; sin embargo, las pacientes con enfermedad recurrente o que precisan tratamiento durante la gestación tienen una supervivencia acortada de aproximadamente 6 meses. El melanoma es el tumor maligno que más frecuentemente metastatiza en la placenta y el feto. Presentamos el caso clínico de una gestante que, con antecedente de melanoma, presentó una recurrencia en el cerebro durante la gestación y falleció a los 21 días del parto sin presentar afectación placentaria ni fetal

The incidence of malignant melanoma during pregnancy has been estimated to be 0.1 to 2.8 per 1,000 pregnancies. In women with a history of melanoma, pregnancy does not seem to increase the risk of recurrence or to negatively influence survival. However, survival is approximately 6 months shorter in women with recurrent disease and those requiring treatment during pregnancy. Malignant melanoma is the most common type of cancer to metastasize to the placenta and fetus. We report the case of a pregnant woman with a history of melanoma who showed cerebral recurrence and died 21 days post-partum, without placental or fetal metastases (AU)