Real-world Performance of a New Strategy for Off-Label Use of Guselkumab in Moderate to Severe Psoriasis: Super-Responder Patients as the Epitome of Efficacy and Optimisation

Background Guselkumab is a drug used to treat moderate to severe plaque psoriasis. However, real-life clinical data on its of-label use are limited, especially regarding the optimal drug dosage regimen for diferent patient profles. Objective The main objective of this real-world, single-centre, retrospective study was to identify the of-label guselkumab dosing regimen used in clinical practice. The study also aimed to evaluate the drug's efcacy, safety, and survival, as well as the proportion of super-responders (SR) based on a newly proposed defnition. Methods The study included 69 patients who started treatment with guselkumab between March 2019 and July 2021. Patients were followed up until April 2022, during which time their efcacy, safety, persistence, and use of guselkumab were recorded. Patients were aged ≥ 18 years and had moderate to severe plaque psoriasis. Results The mean disease duration was 18.6 years, and 59% of patients had received at least one biologic treatment before guselkumab with a mean of 1.3 biologics per patient. The initial absolute Psoriasis Area and Severity Index (PASI) was 10.1 and decreased to 2.1 between Week 11–20 without signifcant changes in the PASI value throughout the 90 weeks of followup. The cumulative probability of drug survival was 93.5% at Week 52. No diferences were found in terms of efcacy and survival associated with the of-label drug dosage regimens compared to the doses described in the Summary of Product Characteristics (SmPC). The greatest adjustments in the drug administration regimen were achieved in the subgroups of bionaïve and SR patients, with a reduction in the number of administrations by 40% and 47% compared to the regimen described in the SmPC. Super-response to guselkumab was mainly associated with patients naïve to previous biologic treatment. Conclusion The study demonstrated that of-label use of guselkumab was safe and efective in real-life clinical practice. The fndings suggest that adjustments to the drug administration regimen may be necessary to optimise its use in diferent patient profles, especially in SR and bio-naïve patients. Further studies are needed to confrm these fnding

NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

Relapse is a major cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT). Treatment options for relapse have been inadequate, and the majority of patients ultimately die of their disease. There is no standard approach to treating relapse after alloHSCT. Withdrawal of immune suppression and donor lymphocyte infusions are commonly used for all diseases; although these interventions are remarkably effective for relapsed chronic myelogenous leukemia, they have limited efficacy in other hematologic malignancies. Conventional and novel chemotherapy, monoclonal antibody therapy, targeted therapies, and second transplants have been utilized in a variety of relapsed diseases, but reports on these therapies are generally anecdotal and retrospective. As such, there is an immediate need for well-designed, disease-specific trials for treatment of relapse after alloHSCT. This report summarizes current treatment options under investigation for relapse after alloHSCT in a disease-specific manner. In addition, recommendations are provided for specific areas of research necessary in the treatment of relapse after alloHSCT

Corrigendum: Reliability and validation of the child eating behavior questionnaire in 3- to 6-year-old Spanish children

A corrigendum on Reliability and validation of the child eating behavior questionnaire in 3- to 6-year-old Spanish children by Jimeno-Martínez, A., Maneschy, I., Moreno, L. A., Bueno-Lozano, G., De Miguel-Etayo, P., Flores-Rojas, K., Jurado-Castro, J. M., de Lamas, C., Vázquez-Cobela, R., Martinez-Lacruz, R., Portoles, O., Martínez, J. A., Navas-Carretero, S., Schröder, H., Fitó, M., Babio, N., Salas-Salvadó, J., Leis, R., Gil-Campos, M., and Rupérez, A. I. (2022). Front. Psychol. 13:705912. doi: 10.3389/fpsyg.2022.70591

TOMOBFLOW: feature-preserving noise filtering for electron tomography

<p>Abstract</p> <p>Background</p> <p>Noise filtering techniques are needed in electron tomography to allow proper interpretation of datasets. The standard linear filtering techniques are characterized by a tradeoff between the amount of reduced noise and the blurring of the features of interest. On the other hand, sophisticated anisotropic nonlinear filtering techniques allow noise reduction with good preservation of structures. However, these techniques are computationally intensive and are difficult to be tuned to the problem at hand.</p> <p>Results</p> <p>TOMOBFLOW is a program for noise filtering with capabilities of preservation of biologically relevant information. It is an efficient implementation of the Beltrami flow, a nonlinear filtering method that locally tunes the strength of the smoothing according to an edge indicator based on geometry properties. The fact that this method does not have free parameters hard to be tuned makes TOMOBFLOW a user-friendly filtering program equipped with the power of diffusion-based filtering methods. Furthermore, TOMOBFLOW is provided with abilities to deal with different types and formats of images in order to make it useful for electron tomography in particular and bioimaging in general.</p> <p>Conclusion</p> <p>TOMOBFLOW allows efficient noise filtering of bioimaging datasets with preservation of the features of interest, thereby yielding data better suited for post-processing, visualization and interpretation. It is available at the web site <url>http://www.ual.es/%7ejjfdez/SW/tomobflow.html</url>.</p

Dietary and Lifestyle Patterns in the Spanish Pediatric Population (One to <10 Years Old): Design, Protocol, and Methodology of the EsNuPI Study

The interest in a healthy diet and lifestyle during the early stages of life increased, pointing out its role in the development of noncommunicable chronic diseases throughout adult life. Dietary habits and dietary patterns begin to be established in early childhood and persist during adulthood. Therefore, the EsNuPI (“Nutritional Study in Spanish Pediatric Population”) study aims to depict the dietary patterns, physical activity, and sedentary behaviors in Spanish children aged from one to <10 years old. This prospective, cross-sectional, observational study recruited a total of 1514 children from Spanish cities with >50,000 inhabitants, stratified by Nielsen areas. Participants were involved in one face-to-face survey, followed by a telephone survey after at least one week. Information about dietary intake and habits was obtained using a quantitative food frequency questionnaire and two 24-h dietary recalls. Physical activity and sedentary behaviors were registered using a specific questionnaire based on a seven-day record. Data were processed and stratified by categorical variables to be statistically analyzed in order to meet the study objectives. This study is the first of its kind in a Spanish reference population of this age range and the first to evaluate whether the consumption of adapted milk formulas and dairy products is associated with healthier dietary patterns and better diet quality and lifestyles in this group.This research was funded by Instituto Puleva de Nutrición (IPN)

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility

Silver Nanostars with High SERS Performance

We report in this work the fabrication, for the first time, of silver nanostars (AgNS) by a simple new method consisting of the chemical reduction of Ag⁺ by neutral hydroxylamine, followed by a capping–reduction process induced by citrate. TEM and SEM were employed to study the morphology of the resulting nanoparticles, which exhibit a star-shaped morphology with a central particle provided with several arms or protuberances with low sharpness in the vertices. Dark field microscopy was employed to study the scattering emission of individual nanostars indicating the increasing presence of nanoparticles with scattering emission toward the red region. AgNS displayed a high performance in surface-enhanced Raman scattering (SERS) applications. The effectiveness of these nanoparticles was probed by using the drug probenecid, leading to intense SERS spectra without the addition of aggregation agents